Synthetic and mechanistic aspects of sulfonyl migrations
Sulfonyl migrations, frequently described as ‘unusual’ or ‘unexpected’, from the last 20 years, including 1,2-, 1,3-, 1,4-, 1,5-, 1,6- and 1,7-sulfonyl shifts, through either radical or polar processes, either inter- or intramolecularly are reviewed.
Mechanistic knowledge and noncovalent interactions as the key features for enantioselective catalysed multicomponent reactions: a critical review
This critical short review focuses on some key features which determine successful enantioselective catalysed multicomponent reactions (MCRs) and are typically underappreciated in the literature.
The importance of N-heterocyclic carbene basicity in organocatalysis
This review highlights the importance of N-heterocyclic carbene (NHC) basicity for transformations in which NHCs are used as catalysts.
On the reciprocal relationship between σ-hole bonding and (anti)aromaticity gain in ketocyclopolyenes
σ-Hole bonding interactions (e.g., tetrel, pnictogen, chalcogen, and halogen bonding) can polarize π-electrons to enhance cyclic [4n] π-electron delocalization (i.e., antiaromaticity gain) or cyclic [4n + 2] π-electron delocalization (i.e., aromaticity gain).
Divergent pathway and reactivity control of intramolecular arene C–H vinylation by vinyl cations
A computational study revealed the mechanistic details and controlling factors of reactivity in intramolecular C–H vinylation through a vinyl cation intermediate.
The optimal DFT approach in DP4 NMR structure analysis – pushing the limits of relative configuration elucidation
What computational methods should be used to achieve the most reliable result in computational structure elucidation? A study on the effect of quality and quantity of geometries on computational NMR structure elucidation performance is reported.
Mechanism of nitrones and allenoates cascade reactions for the synthesis of dihydro[1,2-a]indoles
Quantum mechanical calculations (DLPNO-CCSD(T) and M06-2X) are employed to gain insights into the mechanism and selectivity in the catalytic synthesis of dihydropyrido[1,2-a]indoles from the cascade reaction between nitrones and allenes.
A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam
A simple route to enantiomerically pure (S)-2-aminobutyramide – the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.
Superelectrophilic activation of 1-nitronaphthalene in the presence of aluminum chloride. Reactions with benzene and cyclohexane
Aluminum chloride was successfully used instead of liquid superacids to mediate selective reactions of 1-nitronaphthalene with benzene and cyclohexane.
Experimental evidence for the formation of cationic intermediates during iodine(III)-mediated oxidative dearomatization of phenols
Hammett analysis reveals iodine(III)-mediated oxidative dearomatization reactions proceed through cationic intermediates and not direct nucleophilic attack on an activated phenol.
On the dual reactivity of a Janus-type mesoionic dipole: experiments and theoretical validation
A mesoionic bicycle, easily synthesized from a proteinogenic amino acid, L-leucine, behaves as both thiazolium-olate and diazolium-olate dipoles, as unveiled by its dipolar cycloadditions.
A “cross-stitched” peptide with improved helicity and proteolytic stability
Peptide “cross-stitching” maintains binding affinity and can enhance helical and proteolytic stability.
Raise the anchor! Synthesis, X-ray and NMR characterization of 1,3,5-triazinanes with an axial tert-butyl group
Decomplexation as a rate limitation in the thiol-Michael addition of N-acrylamides
Experimental and computational agreement highlights rate-limiting “product decomplexation” and functional group effects in the thiol-Michael addition, utilized for sequence-defined oligomers.
A fully diastereoselective oxidation of a mesoionic dipole with triplet molecular oxygen
A metal-free oxidation of a mesoionic dipole with atmospheric oxygen triggers a complex cascade reaction through spin intercrossing, as supported by computation, and leading to polycycles with complete diastereoselection.
Influence of phenylpropanoid units of lignin and its oxidized derivatives on the stability and βO4 binding properties: DFT and QTAIM approach
The interference of the phenylpropanoid units (S, G and H) on the properties of the βO4 bond was investigated by the topological analysis via QTAIM and the stability of the lignin and its oxidized structure were studied by the gap analysis
The chemical gymnastics of enterocin: evidence for stereodivergence in Nature
Stereodivergence in Nature encapsulates both enzymatic (biosynthetic) and non-enzymatic (chemical) diversification of natural product scaffolds arising from a single biosynthetic pathway.
Palladium-catalyzed C–H activation of anisole with electron-deficient auxiliary ligands: a mechanistic investigation
In this work, the experimentally observed site-selectivity and ligand choice of Yu's meta-arylation reaction were rationalized through DFT calculations.
The effect of solvation in torquoselectivity: ring opening of monosubstituted cyclobutenes
The paradigmatic electrocyclic ring opening of monosubstituted cyclobutenes has been used to diagnose possible solvation effects tuning the torquoselectivity observed in these reactions.
Understanding the mechanism and reactivity of Pd-catalyzed C–P bond metathesis of aryl phosphines: a computational study
Computational study revealed the mechanistic details and reactivity profile of the Pd/PhI-cocatalyzed C–P bond metathesis of aryl phosphines.
Monophenolase and catecholase activity of Aspergillus oryzae catechol oxidase: insights from hybrid QM/MM calculations
Monophenolase and diphenolase activities of the [Cu2O2]2+ active site of Aspergillus oryzae catechol oxidase are revealed by hybrid QM/MM calculations.
Photochemical [2 + 2] cycloaddition reaction of carbonyl compounds with Danishefsky diene
An efficient oxetane formation has been developed in the photochemical [2 + 2] cycloaddition reaction of benzophenone with Danishefsky diene.
Cross-linking of aromatic phenolate groups by cytochrome P450 enzymes: a model for the biosynthesis of vancomycin by OxyB
Aromatic cross-linking by cytochrome P450 enzymes was studied computationally. P450 Compound I rapidly abstracts two weak phenolic H-atoms that link up via a rate-determining C–O bond formation.
Understanding the structures and aromaticity of heteroporphyrins with computations
Different heteroporphyrins go through two different aromatic pathways, either 18π-annulene or 22π-electron model.
Meisenheimer complexes as hidden intermediates in the aza-SNAr mechanism
In this work we report a computational study about the aza-SNAr mechanism in fluorine- and chlorine-containing azines with the aim to unravel the physical factors that determine the reactivity patterns in these heterocycles towards propylamine.
Chemical transformations of push–pull fluorenones: push–pull dibenzodicyanofulvenes as well as fluorenone– and dibenzodicyanofulvene–tetracyanobutadiene conjugates
We report push–pull fluorenones (FOs) that can be transformed into dibenzodicyanofulvenes (DBDCFs). These FOs and DBDCFs, which contain a CC bond, can subsequently be converted into tetracyanobutadiene conjugates.
The intermolecular anthracene-transfer in a regiospecific antipodal C60 difunctionalization
The topochemically controlled regiospecific antipodal C60 difunctionalization proceeds via an ‘inverted sandwich’ with double-decker π–π-stacking interactions.
Controlling the liberation rate of the in situ release of a chemical fuel for the operationally autonomous motions of molecular machines
Aminolysis of the anhydride of 2-cyano-2-phenylpropanoic acid can be employed to conveniently regulate the liberation rate of the related acid which, in turn, can be used as a fuel for acid–base operated molecular machines.
Origin of the ligand effect in the cobalt catalyzed regioselective hydroboration of 1,3-diene
The detailed mechanism and the origin of the ligand-controlled regioselectivity in the cobalt catalyzed hydroboration of 2-substituted 1,3-diene have been investigated.
Enhanced reactivity of the pyrimidine peroxyl radical towards the C–H bond in duplex DNA – a theoretical study
The peroxyl radical exhibits a much stronger reactivity towards C1′–H1′ in duplex DNA with respect to single-stranded DNA.
Chemo- and regioselective click reactions through nickel-catalyzed azide–alkyne cycloaddition
Nickel-catalyzed [3 + 2] cycloaddition reactions of unsymmetrical alkynes and organic azides afford substituted 1,2,3-triazoles with high levels of chemo- and regioselectivity.
The quasi-irreversible inactivation of cytochrome P450 enzymes by paroxetine: a computational approach
The potency of paroxetine as a P450 inhibitor is mainly attributed to the availability of two active sites on its structure, its compatibility with P450's active site and the ease of its tight coordination to heme iron.
Proof of concept for poor inhibitor binding and efficient formation of covalent adducts of KRASG12C and ARS compounds
Comprehensive molecular modeling and kinetic analysis reveal a novel mechanism of the inhibition of the oncogenic mutant of the “undruggable” KRAS protein.
Free-base porphyrins with localized NH protons. Can substituents alone stabilize the elusive cis tautomer?
The localization of central NH protons in antipodally tetrasubstituted tetraphenylporphyrins suggested that suitable substitutions might also stabilize a porphyrin cis tautomer, a possibility that appears to be supported by DFT calculations.
Examination of pinanediol–boronic acid ester formation in aqueous media: relevance to the relative stability of trigonal and tetrahedral boronate esters
The “inverted” order of stabilities Ktrig > Ktet is observed for pinanediol boronate esters in spite of the existence of the usual strain release effect in the O–B–O angle of the cyclic diol ester.
Elucidation of the atroposelectivity in the synthesis of axially chiral thiohydantoin derivatives
A DFT study is carried out in order to elucidate the racemization and cyclization mechanism as well as the atroposelectivity during the synthesis of 2-thiohydantoins. Computational data shows that the racemization occurs after cyclization with the assistance of triethyl amine.
Base-catalyzed C-alkylation of potassium enolates with styrenes via a metal–ene reaction: a mechanistic study
Base-catalyzed, C-Alkylation of potassium (K) Enolates with Syrenes (CAKES) enables practical synthesis or elaboration of pharmaceutical cores via a thusfar elusive mechanism. Herein, computational (DFT) and kinetic studies back a metal-ene reaction.
Establishing linear-free-energy relationships for the quadricyclane-to-norbornadiene reaction
The kinetics of the thermal quadricyclane-to-norbornadiene (QC-to-NBD) isomerization follows a linear-free-energy relationship when using Creary radical values for a selection of aryl/cyano disubstituted derivatives.
Amplification of the chiroptical response of UV-transparent amines and alcohols by N-phthalimide derivatization enabling absolute configuration determination through ECD computational analysis
Transformation of chiral UV-transparent amines and alcohols to phthalimides enhances their chiroptical response allowing their absolute configuration assignment by ECD computation.
The pKa values of N-aryl imidazolinium salts, their higher homologues, and formamidinium salts in dimethyl sulfoxide
The effects of substitution, ring size and cyclisation on the pKa values of imidazolinium salts, higher homologues and formamidinium salts in DMSO are quantified, considering structural and electronic motifs along with crystallographic analyses.
How does cross-conjugation influence thiol additions to enones? A computational study of thiol trapping by the naturally occurring divinyl ketones zerumbone and α-santonin
DFT calculations show how the kinetics and thermodynamics of thiol additions to enones are affected by incorporation of the enone into a cross-conjugated divinyl ketone moiety.
Kinetic modelling of acyl glucuronide and glucoside reactivity and development of structure–property relationships
Detailed kinetic and transition structure modelling to rationalise the differences in reactivity observed between the acyl glucuronide and glucoside metabolites of a series of phenylacetic acid analogues.
Mechanistic investigation into phenol oxidation by IBX elucidated by DFT calculations
Density functional theory (DFT) at the SMD/M06-2X/def2-TZVP//SMD/M06-2X/LANL2DZ(d),6-31G(d) level was used to explore the regioselective double oxidation of phenols by a hypervalent iodine(V) reagent (IBX) to give o-quinones.
Looking at the big picture in activation strain model/energy decomposition analysis: the case of the ortho–para regioselectivity rule in Diels–Alder reactions
The regioselectivity of the DA reaction is predicted by the ortho–para rule which has been explained from FMO theory. Using DFT calculations and ASM/EDA, we found that the results vary depending the position where it is performed.
The phosphorylation mechanism of mevalonate diphosphate decarboxylase: a QM/MM study
Combined MD and QM/MM studies suggested that mevalonate diphosphate decarboxylase requires two magnesium ions for a phosphorylation reaction.
Mechanism and stereoselectivity of benzylic C–H hydroxylation by Ru–porphyrin: a computational study
Density functional theory calculations of an asymmetric benzylic C–H hydroxylation revealed the steric repulsion between the phenyl group of ethylbenzene and the bulky substituent of the D4-symmetric chiral Ru–porphyrin accounts for the stereoselectivity.
The impact of cation structure upon the acidity of triazolium salts in dimethyl sulfoxide
The effect of structure on the pKa value of triazolium salts in dimethyl sulfoxide is quantified, considering common structural and electronic motifs. Included is the first pKa measurement of a triazolium salt that generates a mesionic carbene.
Electronic effects in tautomeric equilibria: the case of chiral imines from D-glucamine and 2-hydroxyacetophenones
Hammett plots show straightforward relationships for tautomeric equilibria in a new class of chiral imine–enamine structures.
(3S,4R)-3,4-Dihydroxy-N-alkyl-L-homoprolines: synthesis and computational mechanistic studies
This is the first synthetic report of (3S,4R)-dihydroxy-N-alkyl-L-homoprolines described so far.
Systematic characterisation of the structure and radical scavenging potency of Pu'Er tea () polyphenol theaflavin
Resolving the functional 3D structural poses of Pu'Er tea antioxidant theaflavin.
Gold(I)-catalyzed nucleophilic cyclization of β-monosubstituted o-(alkynyl)styrenes: a combined experimental and computational study
The diastereospecific 5-endo cyclization of β-monosubstituted o-(alkynyl)styrenes to 1-functionalized-1H-indenes is reported. The regiospecific generation of a cyclopropyl gold carbene intermediate is also supported by DFT calculations.
Theoretical insights into the E1cB/E2 mechanistic dichotomy of elimination reactions
Modeling the E1cB, E2, and E1cB/E2 borderline mechanisms in terms of carbanion stabilization.
Mechanism of fatty acid decarboxylation catalyzed by a non-heme iron oxidase (UndA): a QM/MM study
QM/MM calculations reveal that the fatty acid decarboxylase UndA employs the FeIII–OO˙− complex to initiate the β-H abstraction with the monodentate coordination mode. The iron center accepts the extra electron of the substrate radical.
An efficient synthesis of benzothiazole using tetrabromomethane as a halogen bond donor catalyst
A CBr4 catalyzed simple, mild, and efficient protocol has been developed for the synthesis of 2-substituted benzothiazole from 2-aminothiophenols and N-methylthioamides under solvent free conditions.
Stereochemistry of spongosoritins: beyond optical rotation
A combination of spectroscopic methods reveals the dependence of the chiroptical properties of spongosoritins on achiral structural features.
Correlating ionic liquid solvent effects with solvent parameters for a reaction that proceeds through a xanthylium intermediate
The effects of ionic liquids on the rate constant of an SN1 process with a xanthylium intermediate differ from those observed for other SN1 reactions. These effects can be correlated to solvent parameters of the ionic liquids allowing predictability.
Understanding the effects of solvate ionic liquids as solvents on substitution processes
The solvent effects of solvate ionic liquids have been compared to the effects of previously studied ‘typical’ ionic liquids for the SN2 reaction between pyridine and benzyl bromide and the SNAr reaction between ethanol and 1-fluoro-2,4-dinitrobenzene.
The mechanism and structure–activity relationship of amide bond formation by silane derivatives: a computational study
The detailed reaction mechanism and structure–activity relationship of substrates in silane reagent-mediated amide bond formation reactions are clarified.
Regio- and chemo-selective cyclization of allenic-Ugi products for the synthesis of 3-pyrroline skeletons
A variety of functionalized 3-pyrroline derivatives were prepared by Ugi post-transformation reaction through cyclization of stable allenic-Ugi products in the presence of base at room temperature.
Neurotransmitter selection by monoamine oxidase isoforms, dissected in terms of functional groups by mixed double mutant cycles
Double mutant cycles were constructed using neurotransmitters and synthetic substrates that measure their selective binding to one monoamine oxidase (MAO) enzyme isoform over another as a function of structural change.
Origins of stereoselectivity in uncatalyzed and ZnBr2-catalyzed Diels–Alder reactions of a chiral sulfinylquinone
DFT calculations show how a chiral sulfinyl group differentiates the diastereotopic faces of an adjacent CC bond in quinone Diels–Alder reactions.
A computational study of regioselectivity in aluminum hydride ring-opening of cis- and trans-4-t-butyl and 3-methylcyclohexene oxides
Nucleophilic ring opening of cyclohexene oxides is known to proceed preferentially through the trans-diaxial pathway (the Fürst–Plattner rule).
Hyperconjomer stereocontrol of cationic polyene cyclisations
The stereochemical outcome of cationic polyene cyclisations of geranylbenzene derivatives is affected by the different reactivity of hyperconjomer intermediates. The synthesis of (±)-taiwaniaquinone G by a cationic polyene cyclisation is described.
Are one-step aromatic nucleophilic substitutions of non-activated benzenes concerted processes?
Analysis of the mechanism of one-step SNAr reactions of non-activated benzenes shows the presence of structures similar to those of Meisenheimer intermediates, thus accounting for the non-concerted nature of these reactions.
Mechanistic insights into ring cleavage of hydroquinone by PnpCD from quantum mechanical/molecular mechanical calculations
QM/MM calculations for ring cleavage of hydroquinone by PnpCD show that Asn258 loses coordination to the iron when the reaction begins. The first-sphere Glu262 can act as an acid–base catalyst to lower the rate-limiting barrier.
First α-deuterium nitroxides; synthesis and EPR study
Herein is reported the first preparation of stable α-deuterium nitroxides of the IAPNO family.
Reaction mechanism of nucleoside 2′-deoxyribosyltransferases: free-energy landscape supports an oxocarbenium ion as the reaction intermediate
The all-atom catalytic mechanism of a nucleoside 2′-deoxyribosyltransferase within its active site using QM/MM methods supports an oxocarbenium species as the reaction intermediate.
Formation of S-alkyl thiophenium ionic liquids: mechanistic rationale and structural relationships
This computational study provides a mechanistic and structural rationale for the synthesis of a new family of S-alkylthiophenium ILs.
Dynamic optical activity induction in the N-alkyl-N′-trityl ureas and thioureas
Stereodynamic trityl group, utilized as a reporter of chirality, hampers hydrogen bonding network in optically active urea and thiourea derivatives.
Cooperativity and serial ligand catalysis in an allylic amination reaction by Pd(II)-bis-sulfoxide and Brønsted acids
Under dual catalytic conditions, the general premise of holding the native ligands on the catalyst throughout the catalytic cycle becomes immediately questionable. We have invoked the likelihood of Serial Ligand Catalysis in an important intramolecular allylic amination of N-Boc protected homoallylic amines leading to an anti-oxazolidinone product.
About this collection
The latest articles published in Organic and Biomolecular Chemistry related to mechanistic, computational & physical organic chemistry research.